This proposal is for continuing support to elucidate and characterize one biochemical lesion accompanying tumorigenesis in mammalian cells. We will investigate progressive alterations of gangliosides of the cell surface. Ganglioside changes correlate with alterations of specific glycosyl transferase activities of ganglioside biosynthesis. The latter are membrane-bound enzymes found with the cell's internal membranes (endomembranes). New work will focus on the regulatory events associated with modulations in glycosyl transferase activities of these internal endomembranes. Early events will be studied with emphasis on the enzymes that catalyze synthesis of precursor glycolipids, enzymes at major branchpoints in the ganglioside biosynthetic pathway, synthesis of sugar nucleotides, and enzymes related to synthesis of sugar nucleotides. Experimental materials will be principally liver tumors of the rat (primary and transplantable) induced with the chemical carcinogen N-2-fluorenylacetamide. Major findings will be verified in induced and transplanted mammary carcinomas and in cell lines derived from these sources and growing in monolayer cultures.